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August 12-15, 2016; San Diego, CA; Day #1 Highlights – Draft

Executive Highlights

Greetings as we take off from sunny San Diego, where enthusiasm abounded at the 43rd annual meeting of the American Association of Diabetes Educators (AADE), which officially began this past Friday. We are continually impressed by the practical and actionable perspectives this meeting features, and moved by the overwhelming sense of care and commitment to improving patient outcomes that permeates each session. See below for our top ten highlights of Day #1 and be sure to check out our highlights from the pre-conference day and our preview for a sneak peak at what’s to come in our future reports – we’ll be bringing you days #2, 3, and 4 in the coming days. Can’t wait? Check out diaTribe’s twitter (@diaTribenews) and Kelly’s Twitter (@kellyclose) for some of our favorite moments!

3. Dr. Robert Vigersky continued his crusade against A1c as the sole “gold standard diabetes outcome,” arguing in favor of a composite metric that paints a more holistic picture of a treatment’s therapeutic value.

6. A session on mobile apps was a mixed bag: TypeZero’s Molly McElwee-Malloy highlighted the dangers of unregulated bolus calculator apps like RapidCalc, while FDA’s Dr. Courtney Lias shared the Agency’s risk-based approach to apps and offered some optimism for using apps in AID devices.

8. Several sessions throughout the day underscored the positive view and immense interest in GLP-1 agonists among diabetes educators and other conference attendees, including an absolutely packed AZ product theater for GLP-1 agonist Bydureon (exenatide once-weekly).

9. In a fascinating panel on obesity medications, Dr. Charmaine Rochester (University of Maryland, Baltimore, MD) expressed a very positive view of Arena/Eisai’s Belviq (lorcaserin), though she did not mention Novo Nordisk’s Saxenda (liraglutide 3.0 mg).

10. We saw 28 companies in the expansive and bustling AADE exhibit hall, headlined by particularly notable updates in technology from Abbott, AgaMatrix, BD, Medtronic, mySugr, One Drop, and Roche.

Top 10 Highlights

1. FDA’s enthusiastic Dr. Courtney Lias expected “we will see an explosion” of automated insulin delivery (AID) systems in the “next couple of years.” She highlighted the Agency’s commitment to efficient regulatory pathways, shared a slide on the “extremely exciting” MiniMed 670G pivotal data, expressed concern over training requirements (a major point of discussion with companies), touched on insurance coverage (companies need to start earlier), maintained high enthusiasm for device interoperability and component AID systems, and offered balanced thoughts on do-it-yourself (DIY) systems like OpenAPS (regulation should move faster so patients don’t feel compelled to do this). Dr. Lias called training one of the “most significant challenges” the AID field will face: “How many of you know what happens when the 670G gets kicked out of closed loop control? Will newly diagnosed patients that start on an AID system understand how to use insulin when the device fails?” This is now a big point of discussion with companies and we’ll be interested to see what the 670G materials look like. Who will have the easiest AID system to train and use in the coming years? Notably, Dr. Lias deliberately used the term “automated insulin delivery (AID)” noting that “artificial pancreas” sets unrealistic patient expectations. We completely agree and love how flexible she is; we hope the entire field changes the terminology too. Looking to the future, Dr. Lias maintained her enthusiasm for device interoperability, standardized device communication protocols, and component AID systems, mirroring her highly positive talks at the NIH Workshop in July, at ADA in mid-June, and the early June Live Q&A Webinar. A lot more from this terrific talk is below, which again reinforced our confidence in and admiration for Dr. Lias and the CDRH team working on CGM and AID.

2. Educators Aimee Jose and Ruth Spirakis (Palo Alto Medical Foundation, CA) argued fervently that “CGM first, pump second” is far easier for patients, less costly at startup, makes providers’ lives easier, and simplifies insulin dose titration. They bluntly characterized the current model of “pump first, CGM second” as “putting the cart before the horse.” The DIaMonD study was not discussed, but they did run through several real-world advantages of starting CGM first: (i) lower startup costs for patients; (ii) CGM is an easier technology to learn first (it is self-started, while pumps require face-to-face training and multiple sessions); (iii) CGM allows improved overnight basal testing: more comprehensive data, more sleep, reduced patient burnout; (iv) CGM requires fewer fingersticks = less work; and (v) CGM enables greater and sooner use of advanced pump features. A series of examples showed how “CGM first, pump second” also helps optimize pump settings with less burden. A CGM-based basal evaluation requires 57% fewer fingersticks (7 vs. 3) and offers 94% more data (120 data points vs. 7 points) than when using fingersticks to drive pump settings in the traditional “pump first” model. In Q&A, Ms. Jose reiterated what we seem to be hearing more and more – having a pump is a personal/lifestyle choice, but sensors should be given to everyone willing to wear them. “When you introduce a patient to CGM, it’s amazing what can happen. As long as they are getting insulin, I don’t care what method they use to deliver it.” It will be interesting to see if this perspective changes once automated insulin delivery is available.

Dexcom talked in its 2Q16 call last week about the “CGM first” message starting to resonate – now ~60% of its new starts are from MDI, an uptick from its historical ~40%, and more in line with the general type 1 population (~70% on MDI).

3.Dr. Robert Vigersky continued his crusade against A1c as the sole “gold standard diabetes outcome,” arguing in favor of a composite metric that paints a more holistic picture of a treatment’s therapeutic value. As he has in the past talks (DTM 2015, ATTD 2016), he began by explaining the NFL QB rating, a single composite number for comparing quarterbacks in professional football (touchdowns, interceptions, completion percentage, and more). Importantly, this metric correlates with outcomes – wins – and he argued for a similar composite metric in diabetes that correlates with positive health outcomes (e.g., extended lifespan and reduced complications). According to Dr. Vigersky, A1c is “woefully inadequate” because it neglects a whole host of crucial factors, and also because it does not immediately reinforce behavior (A1c is an average measure of hemoglobin glycosylation over the three months prior to the test), like a more directly glucose-centric measurement would. There have been a number of suggested formulations for what a composite measure for diabetes outcomes might look like: (i) the glucose pentagon (DT&T 2009 and JDST 2012), a single graph and number combining five elements of glycemia (A1c; SD; time >160 mg/dl; AUC > 160 mg/dl; and mean glucose); (ii) the Q-score (BMC Endocrinologist Diab 2015), a single numerical value combining five primary factors that determine CGM profiles (central tendency, hyperglycemia, hypoglycemia, intra- and inter-daily variations); and (iii) his own novel approach (published last year in JDST) combining A1c, hypoglycemia, and weight change in a single score out of 100. Dr. Vigersky also proposed a novel composite metric that more accurately reflects the hypoglycemic experience – this is still a work in progress, but we hope something comes of it!

4. Powerhouse Ms. Patty Telgener (Emerson Consultants, Excelsior, MN), an annual favorite at AADE, urged healthcare providers to submit feedback on CMS’ proposed regulations surrounding Medicare coverage of DPP during a completely-packed lecture on the current diabetes self-management training (DSMT) reimbursement landscape. The most significant change in DSMT reimbursement over the past year, and the main focus of Ms. Telgener’s talk, was Medicare’s proposed expansion of its coverage to include reimbursement for the Diabetes Protection Program (DPP) beginning in January 2018. Ms. Telgener expressed great enthusiasm for this policy change, highlighting the beneficial public health impact of broader DPP access for the millions of Americans with prediabetes (many of whom rely on Medicare). While in theory this piece of healthcare reform is clearly well-aligned with the incentives of diabetes education, the details of the policy’s implementation remain fairly vague, particularly with regard to the payment model, despite CMS’ recent release of a draft of the 2017 Medicare Fee Schedule that provides an initial look at some guidance. Ms. Telgener passionately and repeatedly urged her audience of physicians and diabetes educators to submit their recommendations to CMS, which is accepting feedback on this matter until September 2016 with a final ruling expected in November 2016. The CMS is also seeking commentary on its proposed Medicare expansion to include coverage for diabetes self-management training (DSMT), a valuable service which, sadly, is “vastly underutilized” according to Ms. Telgener. With policies such as these, the devil is in the details. We couldn’t agree more with Ms. Telgener that insight from diabetes educators will be an instrumental factor in ensuring that the DPP expansion is implemented as effectively as possible. We are particularly concerned about awareness, and hope that Medicare’s final DPP and DSMT coverage policies prioritize this, in addition to measures that make these programs as accessible as possible, both in terms of logistical convenience and affordability. Optimistically, positive health and economic outcomes for the Medicare DPP coverage could help demonstrate the value of investment in diabetes prevention in the prediabetes population – we would love to see commercial and other government payers (Medicaid, VA, etc.) follow the example set by Medicare. Furthermore, perhaps widespread investment in lifestyle interventions for prediabetes could eventually pave the way for reimbursement of pharmacotherapies for prediabetes, such as metformin.

5. In a rousing keynote call-to-action, Dr. Evan Benjamin (Tufts University, Boston, MA) encouraged diabetes educators to (i) advocate locally; (ii) change the narrative; (iii) embrace innovation; (iv) have hope in order to spearhead the shift toward a value-based, patient centered healthcare system. He emphasized that the current volume-based healthcare system, with its rising costs, is unsustainable and called for a “new normal” that focuses on improved care and coordination to optimize the value of healthcare. In particular, he put forth a triple aim framework for healthcare reform involving (i) improvement in the health of the population; (ii) improvement in the experience of care through better coordination and safety, and (iii) lowering the per capita cost. That said, Dr. Benjamin acknowledged the tensions that can often exist between these three aims and emphasized that providers will need to work to find the right balance. To achieve this, Dr. Benjamin advocated for a shift from (i) fee-for-service payment models to global payment models that offer a pre-fixed amount to cover the entirety of an individual or a population’s healthcare; (ii) fragmented care to coordinated care; and (iii) a focus on individuals to a focus on individuals, populations, and communities. He also emphasized the need for a focus on prevention within this new health system – music to the ears of the audience and ourselves. Dr. Benjamin offered several actionable steps that diabetes educators can take to lead the shift toward this new value-based, patient-centered system. He encouraged diabetes educators to advocate locally for prevention and education, urging them to approach local architects of innovative health reform programs and discuss the value and cost-savings of prevention. He asked educators to change the narrative around healthcare provision by implementing shared decision making practices. As he put it, instead of asking “what’s the matter?” providers should move toward asking “what matters to you?” We loved this patient-centered approach and reframing of a classic healthcare question. Dr. Benjamin further asked educators to embrace innovation, highlighting several exciting new models of care delivery that involve telehealth, new payment models, or the forging of new partnerships between providers to improve healthcare novel and unexpected ways. Finally, Dr. Benjamin closed with the simple reminder to have hope and positioned health reform as a new era of opportunities for diabetes educators. Dr. Benjamin’s presentation underscored the need for buy-in from varied healthcare providers – including physicians, diabetes educators, nurses, physician assistants, dieticians, and more – into the benefits of value-based care and the key roles care teams comprised of these professionals will need to play in order to make the transition to a new health system paradigm.

Dr. Benjamin pointed out that healthcare costs in the US continue to grow at unsustainable rates but without appreciably better outcomes than many other countries that spend substantially less. In particular, he emphasized that reliability within the healthcare system is more – for instance, the reliability of a patient receiving appropriate medication after a heart attack is lower than airline baggage handling. He also highlighted the high rate of medical errors in the US (over one million serious preventable medication errors in the US annually) and suggested that a significant portion of these errors can be attributed to overuse of healthcare therapies and treatments, rather than misuse or underuse. He further noted that 30% of healthcare spending in the US goes toward “useless” treatments, costing $600 billion/year, and argued that this situation is the result of a system with misaligned incentives and an emphasis on volume rather than value – as exemplified by the fee-for-service model of healthcare payment. Other factors contributing to higher healthcare costs according to Dr. Benjamin include fragmented care delivery that leads to additional expense and frustration for patients, a lack of transparency on the costs and quality of healthcare, quality defects, rising rates of chronic disease in aging populations, a lack of attention to preventive care, and the structure and supply of providers in the US. On the last point, Dr. Benjamin highlighted the contrast between the US where two-thirds of physicians are specialists and other countries where two-thirds of physicians are primary care doctors.

6.A session on mobile apps was a mixed bag: TypeZero’s Molly McElwee-Malloy highlighted the dangers of unregulated bolus calculator apps like RapidCalc, while FDA’s Dr. Courtney Lias shared the Agency’s risk-based approach to apps and offered some optimism for using apps in AID devices. Ms. McElwee-Malloy noted that 83 unregulated apps currently offer insulin dosing advice, but call themselves “wellness apps,” and are thus illegally marketed. Running through screenshots of RapidCalc (a free bolus calculator), she noted some pretty dangerous stuff: defaulting to mmol/l (changing the setting is really buried) and absurd checkboxes that are confusing or not clinically valid (“BG not measured/extra carbs” are the same check box; “Over 2 units of alcohol in last 4 hours” is confusing – what is a unit of alcohol?). She noted there are only “two” FDA-cleared bolus calculator apps, displaying pictures of Roche’s Accu-Chek Connect and J&J’s OneTouch Reveal app – we’d note that LifeScan’s current OneTouch Reveal app does not have a bolus calculator. WellDoc’s BlueStar does have a bolus calculator, and she was probably referring to the future planned integration of these apps. [Companion Medical’s just cleared InPen also has a bolus calculator in the paired app, though it won’t launch until 2017.] Ms. McElwee-Malloy asked educators to do some homework: Go to the app store, download any diabetes app, and see if you can spot any problems. Do you understand how to use it? When in use, do you consider the advice sound for your patients? What value does this bring to your patients and your practice? We thought this was reasonable advice, though her discussion was fairly negative and absent any app recommendations. There are certainly many unregulated logging apps like mySugr and Glooko that patients DO find useful, and the coming years will undoubtedly see more FDA approved apps that do offer valid dosing advice and treatment recommendations.

Dr. Courtney Lias followed with a balanced review of the FDA’s risk-based approach to mobile app regulation, sharing some optimism for AID. She explained that most apps are unregulated (e.g., logging and tracking, wellness), and regulation focuses on the slice of diabetes apps that communicate with regulated medical devices (e.g., a CGM display app) or provide treatment advice (e.g., a bolus calculator). Regarding automated insulin delivery, Dr. Lias shared that these devices “should be developed with apps in mind” – echoing previous comments from the NIH Workshop. However, remaining technical challenges must be overcome, such as operating system updates, critical functions, and alarms. Dr. Lias called operating system updates “very challenging for manufacturers, particularly for Android devices” where a variety of manufacturers exist, and they do not give developers advanced notice like Apple. Regarding critical functions, companies must determine what happens with mobile medical apps in certain situations: apps running in the background, phone calls interrupting processes, etc. The phone mute button is a particularly difficult challenge – what happens when the phone is on silent and a critical alarm (low CGM) doesn’t sound? Dexcom has talked about updating its app to incorporate this mute override feature, but it is certainly not easy and presumably requires working directly with Apple. We think all of this solvable and salute the FDA for sorting through this very difficult and quickly moving field. The risk-based approach is right on the mark in our view, and we’ll be interested to see how quickly more valuable apps get through the FDA.

7. Dr. Anthony McCall (University of Virginia, Charlottesville, VA) pointed to BeAM (“bedtime-AM”) score as a valuable but often-overlooked metric for nocturnal hypoglycemia risk. BeAM calculates the difference between blood glucose at bedtime and breakfast, with a larger difference/higher score indicating that the individual’s glucose has dropped more significantly throughout the night. Paying attention to this score will thus send a clear, direct signal to a providers and diabetes educators if their patient is at risk for nocturnal hypoglycemia, Dr. McCall explained, as regular large BeAM scores suggest the risk of potential overnight lows. Despite this seemingly intuitive method of assessing the likelihood of overnight lows, very few people in the audience responded that they had heard of BeAM before. We first heard about it at this year’s Keystone conference, where the illustrious Dr. Bruce Bode (Atlanta Diabetes Association, GA) presented BeAM as a useful way to quantify whether or not a new therapy is working for a patient. We’re certainly intrigued by this measurement, especially given its low-cost and easy calculation (patients simply have to subtract two values that they would typically be measuring in any case via fingersticks. [CGM would offer a deeper dive, giving more clarity on when lows were occurring.] We wonder if we’ll start to see BeAM used more often in evaluating diabetes care, especially in the context of basal insulin therapy.

8. Several sessions throughout the day underscored the positive view and immense interest in GLP-1 agonists among diabetes educators and other conference attendees. A packed, standing-room-only An AZ-sponsored product theater on GLP-1 agonist Bydureon (exenatide once-weekly) was completely packed and standing-room-only (indeed, our team at Close Concerns only just barely made it in ourselves!) While the content of the product theater was not particularly notable or new, the sheer volume of attendees is a testament to the massive and growing interest in the use of GLP-1 agonist therapy. In the session, Dr. Robert Busch (Endocrine Group, Albany, NY) emphasized the benefits of Bydureon on A1c reduction, glycemic variability, and weight loss, reviewing several clinical trials of Bydureon with CGM, head-to-head with basal insulin, and compared to twice-daily Byetta (exenatide). The session also featured a video of a diabetes educator demonstrating the (rather complex) dose administration process for Bydureon – we expect this administration will be simplified once the Bydureon suspension formulation is available. On the way out of the session, each attendee was handed a Bydureon training pen for use at home. Indeed, in an earlier session on various pharmacotherapy considerations in patients with chronic kidney disease, there was clear overwhelming support for the initiation of GLP-1 agonists over most other diabetes drug classes. The session involved several case studies as a patient progressed through worsening levels of renal function and asked the audience which of the many available pharmacotherapies they would prefer to apply to the patient. At each opportunity to recommend a therapy within the cases, the room overwhelmingly voted in favor of GLP-1 agonist use.

9. In a fascinating panel on obesity medications, Dr. Charmaine Rochester (University of Maryland, Baltimore, MD) expressed a very positive view of Arena/Eisai’s Belviq (lorcaserin). Dr. Rochester summarized findings from the BLOOM-DM trial, which showed significant weight loss (44% of patients on Belviq dropped at least 5% of baseline weight vs. 16% of placebo patients, p<0.001) as well as significant reductions in A1c (down 0.9% vs. placebo) and fasting plasma glucose (down ~27 mg vs. placebo). In her view, it’s advantageous for patients with type 2 diabetes and obesity that this drug indicated for weight loss also has pronounced benefits for glycemic control. The panel offered limited discussion specific to Saxenda, which is surprising considering that Saxenda currently holds the majority of the obesity market in the US by value (63% of market as measured by revenue) and is growing fast in terms of prescription volume (16% of market as measured by total prescriptions [TRx]). Dr. Rochester further discussed Belviq’s ability to be taken without regard to meals, which makes it more convenient for patients, and pointed out that it requires a lower number needed to treat (NNT) in order to achieve 5% and 10% weight loss in one year compared to orlistat. The panel characterized the emergence of more advanced weight loss medications with more tolerable side-effect profiles as very good news. The bad news, as we see it, is that providers and educators are still often reluctant to consider non-lifestyle modification interventions. When panelists surveyed educators in the audience, there was resounding endorsement of screening for obesity and referring patients to dieticians (we suspect this sampling may be somewhat skewed by the fact that many dieticians attend this meeting). In contrast, only a smattering of hands went up when attendees were asked how many of them would consider a pharmacological intervention if diet and exercise don’t suffice. We enjoyed hearing about the efficacy of available weight loss drugs, and we’re hopeful that commentary like this will soon overcome the ongoing resistance that continues to discourage providers, educators, patients, and families from considering weight loss medications. We’d love to hear more concrete solutions to address the persistent perception that obesity is not a disease that requires medical management and pharmacotherapy. We perceive a high unmet need for education in this arena, as well as a need for better reimbursement of effective obesity drugs that help patients manage weight as well as type 2 diabetes.

10. We saw 28 companies in the expansive and bustling AADE exhibit hall, headlined by particularly notable updates in technology from Abbott, AgaMatrix, BD, Medtronic, mySugr, One Drop, and Roche.We include topline highlights immediately below and full summaries in the detailed Exhibit Hall review. On the drug side, we saw booths ranging from the large and elaborate to the small and sparse from AstraZeneca, GSK, Intarcia, J&J/Janssen, Lilly, MannKind, Merck, Novo Nordisk, and Sanofi.

Abbott showed off FreeStyle Libre Pro (under glass) in a large booth, which is unfortunately still pending PMA approval.

mySugr announced the limited US launch of Coaching in September – watch the intro video here, featuring Gary Scheiner. The product will have an introductory price of $19.99 per month ($39.99 ongoing), leverage the world’s most popular diabetes app (Logbook; 770,000+ registered users), and add a killer iPad Pro interface for educators.

One Drop announced the upcoming launch of One Drop Premium: an impressive ~$30-40 per month cash pay for unlimited test strips, a Bluetooth-enabled BGM, 24/7 in-app CDE coaching, and a “digital therapeutics program” (AADE/ADA-based) in the One Drop app. The meter is currently under FDA review. Premium is expected to ship in October.

Roche confirmed that there are no plans to launch the Accu-Chek Insight CGM in the US anytime soon, and the next device in the US pipeline is the Medingo-acquired Solo patch pump, which is still at least a year out.

Detailed Discussion and Commentary

Courtney Lias, PhD (FDA, Silver Spring, MD)

FDA’s enthusiastic Dr. Courtney Lias expected “we will see an explosion” of automated insulin delivery (AID) systems in the “next couple of years.” She highlighted the Agency’s commitment to efficient regulatory pathways, shared a slide on the “extremely exciting” MiniMed 670G pivotal data, expressed concern over training requirements (a major point of discussion with companies), touched on insurance coverage (companies need to start earlier), maintained high enthusiasm for device interoperability and component AID systems, and offered balanced thoughts on do-it-yourself (DIY) systems like OpenAPS (regulation should move faster so patients don’t feel compelled to do this). Dr. Lias called training one of the “most significant challenges” the AID field will face: “How many of you know what happens when the 670G gets kicked out of closed loop control? Will newly diagnosed patients that start on an AID system understand how to use insulin when the device fails?” This is now a big point of discussion with companies and we’ll be interested to see what the 670G materials look like. Who will have the easiest AID system to train and use in the coming years? Notably, Dr. Lias deliberately used the term “automated insulin delivery (AID)” noting that “artificial pancreas” sets unrealistic patient expectations. We completely agree and love how flexible she is; we hope the entire field changes the terminology too. Looking to the future, Dr. Lias maintained her enthusiasm for device interoperability, standardized device communication protocols, and component AID systems, mirroring her highly positive talks at the NIH Workshop in July, at ADA in mid-June, and at the June 2 Live Q&A Webinar. More from this terrific talk below, which again reinforced our confidence in and admiration for Dr. Lias and the CDRH team working on CGM and AID.

Regarding the MiniMed 670G, Dr. Lias highlighted the pivotal’s encouraging 0.5% A1c reduction alongside the impressive 44% hypoglycemia improvement (presented at ADA). She did not give an approval timeline, even though an attendee asked if it would launch by Medtronic’s stated goal of April 2017. The FDA’s commitment and continued enthusiasm for this device seems encouraging, although regulatory reviews are always hard to predict.

Dr. Lias called training one of the “most significant challenges” the AID field will face: “How many of you know what happens when the 670G gets kicked out of closed loop control? Will newly diagnosed patients that start on an AID system understand how to use insulin when the device fails?” Dr. Lias said there is not yet enough discussion about training requirements, and the FDA is actively talking to manufacturers about it. We were not surprised to hear this after leaving the Dexcom-FDA meeting in July; the Agency is clearly and understandably concerned about provider and patient education for tech that moves into the realm of insulin dosing.

Dr. Lias deliberately used “automated insulin delivery (AID)” throughout her talk, noting, “The term artificial pancreas is going out of vogue.” She rightly noted that “artificial pancreas” sets the wrong patient expectations (e.g., “An ‘artificial pancreas’ device is a cure,” “I don’t have to do anything with an artificial pancreas,” etc.). Dr. Lias said that the field is moving to “automated insulin delivery” or “AID,” and we were glad to see this reflected in her talk’s title. David Panzirer has been a strong advocate of “AID” for a long time, and we see this as a positive move for patients and HCPs. We learned in a fascinating ADA poster that nearly half (42%) of patients think “artificial pancreas” refers to an organ graft; clearly there is a lot of education to do and terminology to define.

Dr. Lias was clear about access challenges and insurance coverage:the FDA encourages manufacturers to think about this early, but they often don’t do it. Dr. Lias said the studies to support coverage are “typically sufficient for FDA as well.” Unfortunately, “Most companies put this off until after FDA approval.” We wonder if the problem is not one of prioritization, but speed: the studies payers want to see may be too time-consuming and costly to run pre-market. We hope companies work with the FDA and payers to find a good middle ground solution – products should ideally have reimbursement in place right when they launch. We hope AID can learn from CGM; certainly there is more published literature at this stage of the field, though there won’t be major outcomes studies once the 670G launches.

“People are doing [DIY, OpenAPS] because they feel they need to do it. We recognize the need for smooth and efficient regulatory pathways to market, including efficient clinical trials. Let’s create a situation so patients don’t feel compelled to do this.” We thought this was an outstanding takeaway on a tricky issue, and is exactly the Nightscout group did with remote monitoring of CGM – push companies and the FDA to move fast and approve safe and effective commercial products. Dr. Lias otherwise reiterated what she has said previously: these home-built products do technically fall under FDA’s regulation as Class III devices, but the Agency will enforce based on risks to the public. Right now the risks of OpenAPS are somewhat low, since the systems require technical know-how to build, and are typically built by highly motivated individuals for personal use (or by a parent for a child). Of course, “distribution” takes many forms (not just selling a device), which is why distributing open source software code moves into regulatory gray area.

“How should you handle patients who come to you with DIY AID devices?” Dr. Lias advised providers in the audience to ask patients the following questions: Do you understand exactly what algorithm is being used? Is it right for you? Have you checked the code to ensure it implements the algorithm correctly? Have you double checked? When new modified versions of code are shared, have you re-validated your entire system before implementing it? Etc.

We think these are equally instructive questions for commercial automated insulin delivery devices. Will patients and providers understand how the algorithms work? Will they be simple to explain and setup? Like all technology, AID will improve over time, and the first systems like the 670G will err closer to traditional pump therapy – requiring setup and pretty far from plug-and-play.

Dana Lewis wrote an outstanding article on this topic here, “Our take on how to DIY closed loop, safely.” The piece highlights things to consider before starting DIY closed loop (e.g., it is not a cure!) and getting started with DIY closed loop (e.g., understand how it works!). It’s a great read, even for companies developing these products and patients that go on the soon-to-be commercialized devices.

Aside from the 670G, Dr. Lias also showed data from BU/MGH’s bihormonal Bionic Pancreas. She noted the strong mean glucose and hypoglycemia results, but cited the lack of an approved glucagon as key challenge for commercialization. Dr. Damiano’s plan, as a reminder, is to get the insulin-only system approved first (pivotal to start 2Q17, PMA submission expected by end of 2017), followed by a longer process to get glucagon approved in the device (longer pivotal starting in mid-2017 to gather chronic exposure data, PMA submission perhaps by early 2019).

Echoing her talks at the at the NIH Workshop in July and at ADA in June, Dr. Lias admitted that the current regulatory process will hamper AID innovation – it is suboptimal for devices requiring different manufacturers (e.g., Dexcom/Tandem). The Agency is “working on policies to foster innovation,” and ideally, drive toward component AID systems. The ultimate vision is an ecosystem of devices and algorithms that can talk to each other, but not require approval for every combination. Patients would be able to swap different sensors, algorithms, and pumps in and out as they please (more choice, more innovation), while companies won’t be hampered by legal contracts and lengthy PMA submissions. Dr. Lias shared some of the challenges that must be ironed out:

Standardized communication between devices. She cited the interoperability example of viewing digital pictures on any device from any manufacturer – it just works. [Top of the hat to Tidepool’s Howard Look for sharing this at the FDA Workshop in November 2014, and clearly, influencing the Agency’s thinking.] We hope the FDA can strongly encourage companies to adopt the device communication standards developed in Toronto (Dr. Joe Cafazzo and Melanie Yeung).

Device failure – who is responsible? When something goes wrong in a component system, is the algorithm developer, CGM developer, pump developer, or no one responsible? The regulatory expectations have to be defined on this question. This does sound like a solvable problem to us.

Device modifications. The slide showed a picture of the iPhone 3 vs. iPhone 4 adaptor change. Device standards, said Dr. Lias, will help identify methods and criteria to validate modifications – and presumably, to integrate them quickly into devices. (We’d point to the iPhone adaptor change as a great example of a device modification that killed an innovative product like AgaMatrix’s iBGStar.) We hope this becomes easier with Bluetooth devices that don’t require hardware connections. Still, this will be a concern for AID as CGM continues to rapidly evolve, as algorithms improve, and as pumps change – where will the FDA set the regulatory bar for device changes and updates? How can companies ensure safety, but not need a lengthy PMA submission for every update? How can the FDA promote innovation, but ensure the updated product components are safe and work together well?

What type of data should be used? Sensor values? Glucose concentrations? Etc.

Looking Beyond A1c as the Gold Standard Diabetes Outcome

Looking Beyond A1c as the Gold Standard Diabetes Outcome

Robert Vigersky, MD (Medtronic, Washington, DC)

Dr. Robert Vigersky continued his crusade against A1c as the sole “gold standard diabetes outcome” – we previously heard from him on this topic at DTM 2015 and ATTD 2016 – arguing in favor of a composite metric that paints a more holistic picture of a treatment’s therapeutic value. As he has in the past talks, he began by explaining the NFL QB rating, a single composite number for comparing quarterbacks in professional football (touchdowns, interceptions, completion percentage, and more). More importantly, this metric correlates with outcomes – wins – and he argued for a similar composite metric in diabetes that correlates with positive health outcomes (e.g., extended lifespan and reduced complications). According to Dr. Vigersky, A1c is “woefully inadequate” because it neglects a whole host of crucial factors, and also because it does not immediately reinforce behavior (A1c is an average measure of hemoglobin glycosylation over the three months prior to the test), like a more directly glucose-centric measurement would.

There have been a number of suggested formulations for what a composite measure for diabetes outcomes might look like: (i) the glucose pentagon (DT&T 2009 and JDST 2012), a single graph and number combining five elements of glycemia (A1c; SD; time >160 mg/dl; AUC > 160 mg/dl; and mean glucose); (ii) the Q-score (BMC Endocrinologist Diab 2015), a single numerical value combining five primary factors that determine CGM profiles (central tendency, hyperglycemia, hypoglycemia, intra- and inter-daily variations); and (iii) his own novel approach (published last year in JDST) combining A1c, hypoglycemia, and weight change in a single score out of 100. The audience quickly picked up on the flaw with the glucose pentagon – it didn’t include hypoglycemia! Dr. Vigersky revealed that he has been collaborating with the pentagon’s creator, Dr. Andreas Thomas (Medtronic, Meerbusch, Germany), to replace/add a vertex of the pentagon with hypoglycemia. There are, as Dr. Vigersky put it, “at least a dozen hypoglycemia metrics”, so he proposed a novel composite one. This is still a work in progress and we look forward to what comes of it!

Dr. Vigersky believes that we can leverage big data to determine whether a given proposed metric correlates positively with short- and long-term outcomes. It is theoretically possible to test any new composite metric on the vast quantity of existing clinical data. The alternative would be a time-consuming and expensive outcomes trial, so we were glad to hear him say this. If the FDA agrees with Dr. Vigersky, then the next step will be to standardize which trials the metrics are to be tested on. But for now, baby steps!

As a reminder, the FDA will host a public workshop, featuring Dr. Vigersky, Kelly Close, industry, and other members of the Diabetes Community, entitled “Diabetes Outcome Measures Beyond Hemoglobin A1c” on August 29th. The event will be free and open to the public, but registration must be completed before August 24th. In addition, seating is limited, so sign up soon if you’re interested (you can register here)! Please let us know if you have any questions that you would like to see discussed at the forum!

The Value of Retrospective CGM Data in Shared Decision Making (Supported by Abbott Diabetes Care)

The Value of Retrospective CGM Data in Shared Decision Making

Ms. Davida Kruger and Ms. Virginia Valentine, two dynamos of the CDE world, championed Dr. Rich Bergenstal and colleagues’ one-page, standardized Ambulatory Glucose Profile (AGP), declaring that it is (or at least should be) the new standard of care for interpreting glucose data. Under the current standard, they noted, fingersticks result in inconsistent testing and recording, inadequate pattern-detection during office visits, varying meters/displays, and an oversimplified representation of a patient’s blood glucose profile. In short, it’s a total nightmare, and other areas of medicine like cardiology have figured this out. The AGP provides a digestible, unabridged picture of 14 days of blood glucose data – both graphed and sorted into key statistics (see our deep dive from the JDST/DT&T publication two years ago here). Ms. Kruger and Ms. Valentine talked about how easy it is to dive into AGP data, identify trends, and pull out actionable insights – and many times, patients love problem solving in tandem and figuring out where they can improve their regimens. We look forward to seeing how this session evolves once FreeStyle Libre Pro is approved (still pending PMA approval; submitted over one year ago in 2Q15).

We would love to see even more companies adopt AGP. Abbott paved the way by including it with the FreeStyle Libre download software, and at ADA,we learned that Roche, Diasend, and Glooko signed agreements to add it. As of June, Dr. Bergenstal told us three other device companies and aggregators were expected to sign similar agreements in “the next month” – the big glucose monitoring players that have not signed on yet include Ascensia, Dexcom, J&J/LifeScan, and Medtronic.

Hypoglycemia in 2016: Detection, Consequences, and Prevention

Anthony McCall, MD (University of Virginia, Charlottesville, VA)

In a talk heavily focused on nocturnal hypoglycemia, Dr. Anthony McCall (University of Virginia, Charlottesville, VA) pointed to BeAM score as a valuable but often-overlooked metric for nighttime hypoglycemia risk. BeAM calculates the difference between blood glucose at bedtime and breakfast, with a larger difference/higher score indicating that the individual’s glucose has dropped more significantly throughout the night. Paying attention to this score will thus send a clear, direct signal to a providers and diabetes educators if their patient is at risk for nocturnal hypoglycemia, Dr. McCall explained, as regular large BeAM scores suggest the risk of potential overnight lows. Despite this seemingly intuitive method of assessing the likelihood of overnight lows, very few people in the audience responded that they had heard of BeAM before. We first heard about it at this year’s Keystone conference, where the illustrious Dr. Bruce Bode (Atlanta Diabetes Association, GA) presented BeAM as a useful way to quantify whether or not a new therapy is working for a patient. We’re certainly intrigued by this measurement, especially given its low-cost and easy calculation (patients simply have to subtract two values that they would typically be measuring in any case via fingersticks. Of course, CGM would give a deeper dive in when lows are occurring, but since so few are on it, BeAM has a place. We wonder if we’ll start to see it used more often in evaluating diabetes care, especially in the context of basal insulin. Dr. McCall went on to summarize data on how CGM affects the magnitude and frequency of hypoglycemia both during waking and sleeping hours. He highlighted the “big ray of sunshine” DIaMonD trial presented at ADA 2016, which reported a 79% lower risk of nocturnal hypoglycemia for Dexcom CGM users vs. standard of care (p=0.005), alongside improvements in A1c, time in range, and overall frequency of hypoglycemia. Looking ahead, Dr. McCall suggested that insulin pumps and artificial pancreas devices will be the optimal way to minimize hypoglycemia and especially nocturnal hypoglycemia, expressing early enthusiasm for Medtronic’s just approved MiniMed 630G (threshold suspend on the new pump platform) and the 670G under FDA review.

“We thought the artificial pancreas was ‘around the corner’ 40 years ago, and it’s actually very close now!” Following a detailed discussion of all the complicated factors that make nocturnal hypoglycemia difficult to diagnose and treat, Dr. McCall ended his talk on an optimistic note, reminding the audience that an artificial pancreas device – Medtronic’s MiniMed 670G/Enlite 3 hybrid closed loop – will potentially be commercially available by 2017 (submitted in June).

Questions and Answers

Q: What about a person who works the night shift, sleeping during the day and working at night? This skews circadian rhythms. Does this patient face the same risks for nocturnal hypoglycemia?

A: Fragmented sleep often causes patients to be more insulin-resistant. I find myself writing letters to employers to get my patients on a standard shift to help with their glycemic control. Do you know which employers I struggle with the most? Hospitals.

Comment: I’m mostly talking about nonprofessionals, people who may not have any flexibility in their working hours. With the job market as it is…

A: In that case, I simply have patients shift the way they take their insulin, timing it with their “day.” Strategies using CGM, AP, model predictive control – these things are also going to help. I’m hoping that CGM will be approved and reimbursed by Medicare. Please?

This panel outlined the advantages of weight loss drugs, with Dr. Charmaine Rochester (University of Maryland, Baltimore, MD) expressing a very positive view of Arena/Eisai’s Belviq (lorcaserin) and describing the benefits of modest weight loss goals. Dr. Rochester summarized findings from the BLOOM-DM trial, which showed significant weight loss (44% of patients on Belviq dropped at least 5% of baseline weight vs. 16% of placebo patients, p<0.001) as well as significant reductions in A1c (down 0.9% vs. placebo) and fasting plasma glucose (down ~27 mg vs. placebo). In her view, it’s advantageous for patients with type 2 diabetes and obesity that this drug indicated for weight loss also has pronounced benefits for glycemic control. Dr. Rochester further discussed Belviq as an agent that can be taken without regard to meals, which makes it more convenient for patients, and that requires a lower number needed to treat (NNT) in order to achieve 5% and 10% weight loss in one year compared to orlistat. On that note, Dr. Amanda Stahnke (UMKC School of Pharmacy, Kansas City, MO) pointed out that although orlistat has been on the market the longest, it’s unpopular among patients and prescribers due to bothersome side-effects, from GI disturbances to oily stools. The panel characterized the emergence of more advanced medications with a more tolerable side-effect profiles have emerged for the treatment of obesity as very good news. The bad news, as we see it, is that providers and educators are still often reluctant to consider non-lifestyle modification interventions for weight loss.

When panelists surveyed educators in the audience, there was resounding endorsement of screening for obesity and referring patients to dieticians. That said, we suspect this sampling may also be skewed by the fact that many dieticians attend this meeting. In contrast, only a smattering of hands went up when educators were asked how many of them would consider a pharmacological intervention if diet and exercise don’t suffice. We enjoyed hearing about the efficacy of available weight loss drugs, and we’re hopeful that commentary like this will soon overpower the ongoing resistance that continues to discourage providers, educators, patients, and families from considering weight loss medications. We’d love to hear more ideas for concrete solutions to address the persistent perception that obesity is not a disease that requires medical management and pharmacotherapy. We perceive a high unmet need for education in this arena, as well as a need for better reimbursement of effective obesity drugs that help patients manage weight as well as type 2 diabetes.

Dr. Rochester stated that we must set reasonable expectations for weight loss (~5-15%) in order to see long-term success. Admittedly, losing 5% of baseline body weight isn’t nearly as exciting as dropping to half your size – this, according to Dr. Rochester, is why people watch The Biggest Loser. But she pointed out that most contestants on the reality TV show are unable to maintain their weight loss long-term. Dr. Rochester outlined an acceptable definition of successful weight loss: a ~5-15% reduction from baseline body weight that improves a patient’s blood pressure and cholesterol and makes type 2 diabetes easier to manage or prevents the onset of type 2 diabetes in people with prediabetes.

Very surprisingly, there was little discussion specific to Novo Nordisk’s Saxenda (liraglutide 3.0 mg for obesity). At the very end of the session, Dr. Jessica Kerr (SIUE School of Pharmacy, Edwardsville, IL) made a comment about GLP-1 agonists being popular in the diabetes field. This is especially surprising considering that Saxenda currently holds the majority of the obesity market in the US by value (63% of market as measured by revenue) and is growing fast in terms of prescription volume (16% of market as measured by total prescriptions [TRx]).We wonder if the lack of attention to Saxenda may be driven by its relatively new status on the market, by aversions to various aspects of the product (its high cost, injectable nature), or by panelists wanting to provide education on lesser-known obesity drug options.

The data Dr. Rochester presented from Drugs in Context shows that Vivus’ Qsymia (phentermine/topiramate extended-release) actually requires the lowest NNT, followed by liraglutide. A lower NNT value corresponds to better efficacy in achieving 5% or 10% weight loss in one year on the drug. We were surprised to see this given Saxenda’s domination of the obesity market by value (63%) right now and its growing popularity, although admittedly, Saxenda is much more expensive and still holds less than half the market by total prescription (TRx) volume compared to Qsymia (16% vs. Qsymia’s 37%). We’re very curious to see how J&J’s phase 2 canagliflozin/phentermine combination for obesity will fare in terms of NNT, given that SGLT-2 inhibitors are considered to cause greater weight loss than GLP-1 agonists and phentermine is a potent component of Qsymia. We also look forward to learning the NNT for Novo Nordisk’s next-generation GLP-1 agonist semaglutide for obesity (in phase 2 trials), given the company’s repeated statements that semaglutide is a more efficacious drug that liraglutide.

Dr. Lisa Meade (Wingate University, NC) called attention to Qsymia’s efficacy in her talk, highlighting its mechanism of action. She explained that phentermine and topiramate have powerful complementary effects. Phentermine is released immediately from the capsule and suppresses appetite, while topiramate is released after a delay to prolong feelings of satiety. That said, Dr. Meade acknowledged that participants in the CONQUER trials demonstrating Qsymia’s efficacy were 90% Caucasian, suggesting that it may be important to investigate this agent and others in its class with a more diverse patient population.

Importantly, although all four speakers called for more consideration of obesity drug therapies, they emphasized that diet, exercise, and behavior change should absolutely accompany medication. The optimal regimen for weight management, they asserted, is comprehensive care that incorporates healthy lifestyle modifications always and obesity drugs when indicated.

Exhibit Hall

Abbott

Abbott’s booth drew AADE attendees in with its familiar oversized monarch butterfly flapping from the rafters, bright yellow coloring, and a remarkable sugar sculpture of buildings from across the US. Similar to the what we saw at ADA, the booth sported a rotating circular sign reading “FreeStyle Libre Pro”, marking the second major US conference at which the device was displayed under glass. Signs footnoted, “Pending PMA approval,” in line with comments from the July financial update that expected approval imminently. It is unfortunate that approval for the retrospective, blinded system has taken more than a year at this point (submitted in 2Q15)! FreeStyle Libre has yet to be submitted to the FDA, which makes the new 1Q17 US launch goal highly ambitious (implying a ~6-7-month review at most for the first factory calibrated sensor in the US; see the July financial update). There were no additional updates on pipeline front, but reps and booth infrastructure seemed devoted to disseminating as much information as possible about the Pro – numerous booth-goers were of course unaware of the yet-to-be-approved product, which should hopefully end soon. There was also a sliver of the booth dedicated to LibreView, Abbott’s new data management software that we saw at ADA.

AgaMatrix

The AgaMatrix booth showed off the FDA-cleared Jazz Wireless 2 Bluetooth-enabled BGM and paired app (picture below). Reps told us the goal is to launch within a month, and educators came by in a steady stream to pick up a free meter. We got one too and were impressed with the meter’s tiny size (USB-like) and streamlined design (harkening back to the iBGstar – everything is about the app). AgaMatrix is working out the details of a co-pay buy-down program, ideally offering a 30-day supply of strips for $15. We got a first look at the paired AgaMatrix Diabetes Manager app (Android, iOS), which had a streamlined and simple interface and a nice color-coded statistics & logbook export (easy to send to a provider or even integrated into EMR systems). The app (like Dexcom Share) also sends and receives notifications to care providers, friends, and loved ones (“Zoe Shaw measured 102 mg/dl”).

The app’s automatic smart reminder feature is something we hope all BGM companies will add – These reminders can be time- and/or event-based and are configurable. For example, “Test glucose 2 hours after a hyperglycemia event,” “15 minutes after a hypoglycemia event”, or add a custom option (“Bolus 15 minutes before breakfast.” (Most reminder features in diabetes apps are less specific; we love the focus on automatic reminders that only appear after hypoglycemia/hyperglycemia.)

AscenciA

The Contour Next BGM portfolio – Next, Next EZ, and Next Link (wirelessly communicates with Medtronic pumps and uploads to CareLink software via USB) – were heavily featured in Ascencia’s booth. The Next Link was a significant focus, especially given the just-approved MiniMed 630G and capability of remote bolusing from the meter. A soon-to-be-activated web page, Contour Next Concierge on demand, was also introduced at AADE. The site will streamline online ordering of sample meters, strips, educational materials, and more for clinicians. [As an aside, we have been impressed with Ascensia’s DTC cash-pay pricing on Amazon, with 100 strips costing a remarkably low $19.] Reps were giving away popular educational posters featuring information on hypoglycemia, diet, AACE and ADA goals for glycemic control, and A1c-blood glucose correlates.

AstraZeneca

AZ recently extended its free Fit2Me app to include helpful resources for patients with or at risk for cardiovascular disease, and accordingly, Fit2Me was a huge focus of the company’s exhibit hall presence. In addition to its main exhibit, which heavily promoted the resource program, AZ had a second exhibit toward the back of the hall dedicated exclusively to Fit2Me. A prominent overhead sign advertised Fit2Me and Fit My Fridge. A tall monitor at the heart of the main exhibit allowed conference attendees to learn more about how this app works – for example, users can enter information about the ingredients in their refrigerator, how long they want to spend cooking, etc. and the program will output an enticing photo and instructions on how to cook the healthy, diabetes-friendly meal. The exhibit dedicated to Fit2Me featured a large mock-up of the famous Fit2Me food truck and served healthy slushie samples. The floor was made to look like bright green grass. As people slurped slushies, they were encouraged to download the app on site. Multiple slogans on display described the personalized advice that the app provides to patients with diabetes, and now other chronic diseases, including “my plan, my way,” and “a plan in my hand!” AZ’s other products were somewhat sidelined by the promotion of Fit2Me. One corner of the company’s main exhibit was dedicated to GLP-1 agonist Bydureon (exenatide once-weekly), with small monitors, handouts, and information on how providers can help patients access a 90-day prescription of Bydureon for just a $25 copay. The company’s other major diabetes products (SGLT-2 inhibitor Farxiga [dapagliflozin], SGLT-2 inhibitor/metformin combination Xigduo [dapagliflozin/metformin], DPP-4 inhibitor Onglyza [saxagliptin], DPP-4 inhibitor/metformin combination Kombiglyze [saxagliptin/metformin], and GLP-1 agonist Byetta [exenatide twice-daily]) were listed on the overhead sign, but were otherwise not featured within the exhibit.

BD

As promised pre-conference, BD debuted the innovative MiniMed Pro infusion set with FlowSmart technology for the first time in a hall. We thought this would’ve been a great opportunity to bring “Lipo Larry” (the classic lipohypertrophy dummy) out of retirement, but settled for faux-tummies on which to test the new infusion set. Reps said that feedback was extremely positive – patients and providers repeatedly asked how and when they could get their hands on one. BD previously announced that there will be a small (at least 1000 patients, ~three months) initial launch of the set in the US and France to gather feedback, followed by the full scale global rollout, likely by December. At the moment, there is no test drive program in place, but BD will send sample boxes to clinicians so they can allot individual units for patients to try. As a reminder, the set will be made available for Medtronic and non-Medtronic pumps (Animas, Roche, Tandem), though Medtronic will control distribution in both cases.

The booth also called attention to FITTER, last October’s forum about best practices for injection, insulin safety, and infusion sets. Recommendations will be published in a top American medical journal next month. We found out that the recommendations will even include best practices for the Pro-Set side-port catheter. Granted, these may change as more information is gathered from the launch.

BD brought back the immersive virtual reality experience about injection technique from ADA. The two demos allowed us to experience an injection technique counseling session as a patient with type 2 diabetes who had just been instructed to go on insulin, with one video documenting common mistakes physicians make and the other documenting best practices. We love seeing next-gen consumer technology brought into diabetes – VR is all the rage in Silicon Valley, and we wonder how it could be leveraged in diabetes education (either for providers or patients).

DarioHealth (formerly LabStyle)

DarioHealth reps (who were happy about the name change, commenting that it “makes much more sense”) reported that the Android version of the BGM smartphone app will be first approved for Samsung phones, followed by other Android phones. No timeline was provided for either launch. They also mentioned that they had heard rumors of expansion into Italy and South America soon, but couldn’t provide concrete details. The smartphone BGM (headphone jack) system is currently in the US, UK, Netherlands, New Zealand, Australia, and Canada. Version 3.2 of the iOS app, recently launched, includes a number of simple, user-friendly modifications, and the next version, 3.3 is slated for a Q3 launch. Reps also spoke about the company’s mission to better engage the type 2 community, but offered no further details.

Dexcom

Though AADE 2016 is in its hometown, Dexcom opted for a very small booth this year (it was actually dwarfed by Tandem’s neighboring exhibit). Two smartphones showed of G5 mobile, though we spent our time talking to the reps about the positive July 21 FDA panel vote for non-adjunctive use of G5. Reps were clearly excited about the vote, and reiterated one of our big takeaways from the panel and Dexcom’s subsequent 2Q16 call – there are a number of training details to hammer out. We believe this approval is a matter of “when” rather than “if,” though it’s hard to know how long the FDA negotiations will take. Reps did point us to a newly published 52-week, four-arm trial (n=65; Soupal et al., DT&T 2016), offering a highly positive takeaway for Dexcom: adding CGM to MDI drove a similar A1c reduction as adding CGM and a pump (-1.2%; baseline: 8.3%). Further, adding a pump alone (without CGM) only drove a 0.5% reduction in A1c (baseline: 8.4%). Though the study was very small (n=12 on CGM+MDI, n=15 on CGM + pump, n=20 on pump alone, and n=18 on MDI + SMBG), it was great to see the long length and four arm design. The results confirm the preliminary findings from the DIaMonD study (presented at ADA), and what the field has long known – CGM offers significant benefits to MDIs.

Diasend

DiaSend’s modest booth featured a couple of monitors showing off the universal web-based data management platform, with reps demoing the product’s impressive device compatibility (140+). The company recently adopted part of the standardized, one-page Ambulatory Glucose Profile (AGP) – the key modal day graph – and management is in talks to integrate the rest of the very helpful views and statistics. Educators occasionally approached reps to ask questions about how to do something within the platform (such as fixing mis-calibrated time stamps), but these matters were quickly resolved, and the majority of feedback that we heard was overwhelmingly positive. Diasend gets great remarks from most who use it, and we hope the company can continue to drive better insights and pattern recognition (which currently lags behind other data download platforms in our view). In an earlier session, President Mr. Richard Laurits alluded to an upcoming initiative focused on type 2 patients – aptly named “Project Type 2” – but reps didn’t comment on the program.

Glooko

Glooko featured the same capabilities it showed in June at ADA, highlighting its next-gen work to optimize insulin dosing: the DreaMed MD Logic Pump Advisor partnership (study starting later this year) and its Mobile Insulin Dosing System for type 2s (studies in 2H16; launch in 2017). Medtronic integration is in final testing and expected to launch within the next month, just slightly behind the July expectation at ADA. The team demonstrated the Medtronic integration live to visitors to its booth – great to see this is coming imminently, and boy has it been a long time coming. Glooko won praise from expert CDE Gary Scheiner on Saturday, who highlighted the new pump and CGM insight features (e.g., linking infusion set wear time to glucose values). Glooko is now in 1,300 health systems throughout the US, a clear victory following the partnership with Insulet in January. Based on comments from both companies, this seems to be going incredibly well. Reps eagerly spoke about being “device agnostic,” and shared enthusiasm for a CDE User panel – on the desk was a signup sheet for educators who wished to participate in a feedback session.

Glytec

A Glytec rep we spoke with was very enthusiastic about uptake of Glucommander, the cloud-based inpatient insulin dosing software now utilized in 130 hospitals in the US. When asked if the company had any plans to expand to OUS anytime soon (Glucommander received a CE mark last year), he said that it has its hands full stateside, and doesn’t have the infrastructure, nor the staffing, to commercialize in Europe just yet. We were under the impression that Glytec would look to start international efforts this calendar year, but it’s possible that stateside demand has occupied more resources than anticipated. There were no updates on expanding outpatient use of Glucommander, which impressed us in a late-breaker at ADA – a 2.7% A1c reduction (baseline 10.3%) in a 41-patient, uncontrolled, 3-month study at Dr. Bruce Bode’s clinic in Atlanta.

GSK

GSK’s very small booth – squeezed between dLife and Dannon in a long row of other booths – was essentially entirely occupied by a small Medical Information desk staffed by just two representatives. The booth had no flashy advertisements for its GLP-1 agonist Tanzeum (albiglutide), though a LCD screen did display information on several ongoing clinical trials for the product, noting that many were still recruiting. Overall, the small booth from a very large and well-financed company suggested that GSK does not consider diabetes to be a major area of focus.

InSpark Technologies

InSpark reps revealed that Vigilant, the Android and iOS blood glucose pattern recognition app, is no longer exclusively compatible with Accu-Chek CONNECT meters, but any that upload data to platforms such as Apple’s HealthKit. This is a win for BGM users looking for insights into upcoming periods of risk. We reported at ADA that Vigilant will move to a low-cost subscription model, but a rep told us that they now plan to move to a model in which payers cover the cost – this is great to see, since patients are loath to pay for things. On the strategic front, the company is making strides to focus on population health (i.e., a provider can look at a population overview to determine which patients are at risk for short- and long-term complications).

Insulet

Insulet’s fun booth showed off the company’s new branding in a major way – the feel was markedly less corporate than the Insulet of a few years ago. The pod demo kits have changed a bit, now giving HCPs a clear OmniPod so they can see exactly what’s inside the device. (Apparently this is a frequent question.) Reps handed out popcorn and attendees took pictures with Toby the Turtle, Insulet’s new mascot (the shell looks like a pod, and like the OmniPod, turtles can be in water or on land). iPads demoed the educational storybook app launched at FFL, which has received positive reviews from adults with type 1 (to show their kids) and school nurses. Reps seemed excited about the next-gen PDM, but could not offer further details or timing. Per Insulet’s 2Q16 call two weeks ago, it will “debut” at ADA 2017 (not clear if this means approved or just shown for the first time).

Intarcia

Intarcia’s double-sided booth was all about attracting people to its technology and to its mission, emphasizing innovation, disruption, and rebirth. On one side, the company demonstrated the insertion and removal of its newly-branded Medici drug delivery system (the mini-pump used for the delivery of Intarcia’s implantable GLP-1 agonist exenatide ITCA 650). Doubling down on the background of the Medici name, the system featured the tagline “Renaissance of medicine delivery in chronic disease.” A representative shared that Intarcia hopes to attract pharmaceutical partners to develop additional therapeutics for delivery via the Medici system. However, the representatives were unable to discuss ITCA 650, other potential therapeutics, or anything related to the patient experience of implantation and removal and quickly directed visitors to medical affairs when such topics arose. On the other side of the booth, Intarcia proclaimed “Dare 2 Disrupt!” and invited job applicants to join the company. The recruitment is a testament to the rapid expansion of the company – growing from ~50 to ~250 employees in five years, according to a representative. Intarcia is seeking certified diabetes educators in particular to work closely with physicians and in anticipation of the launch of a patient support program.

J&J/Janssen

J&J dedicated about half of its expansive space near the center of the exhibit hall to Janssen products SGLT-2 inhibitor Invokana (canagliflozin) and SGLT-2 inhibitor/metformin fixed-dose combination Invokamet (canagliflozin/metformin). The overhead sign announced in bold letters that Invokamet is now approved as a first-line therapy, highlighting a recent expanded indication granted by the FDA. A few clinical data-heavy, outward-facing displays demonstrated superior A1c lowering from Invokana vs. DPP-4 inhibitor Januvia (sitagliptin), but much of the exhibit was focused on a patients support app called “Check Your Numbers.” Conference attendees could see what the app looks like on an iPad and interact with the interface. Representatives highlighted some of the app’s most helpful features: (i) patients can monitor their medications and are better able to stick to their regimen; (ii) providers can print out materials for patients who are less tech savvy; and (iii) the app is integrated with J&J’s CarePath program that streamlines the prior authorization process for providers.

J&J Lifescan/Animas

LifeScan brought back the pillars encouraging booth-goers to think about the biggest challenges they face as patients and providers (e.g., time, adherence, access, coordination, other) that we saw at ADA, once again giving reps the opportunity to share how the LifeScan portfolio could address these concerns. While the Animas pump business had the lion’s share of visitors, a few attendees spoke with the LifeScan about the One Touch Verio Flex, just launched this past February with an updated OneTouch Reveal app. A rep shared that Reveal version 3.0, featuring tweaks based on user feedback, will be available as soon as 4Q16, but more likely in 1Q17. There were no updates on the One Touch Via bolus-only insulin delivery patch device – we still anticipate the device to be commercially available in select markets outside the US by late 4Q16 and in the US soon thereafter in early 2017, per ADA 2016. Reps in the bustling Animas section excitedly told patients about the G4-integrated Vibe system. As a reminder from July’s Keystone Conference, a single-arm pivotal trial beginning in 4Q16 will test Animas’ next-gen hypoglycemia-hyperglycemia minimizer with Dexcom’s G5 CGM in 200 adults, adolescents, and pediatrics, slating the product for a November 2017 – May 2018 launch.

Lilly

Lilly’s booth drew quite a crowd toward the fresh-squeezed lemonade stand located in the center of the booth. Information on its various products radiated outward from the central lemonade stand in an almost flower-like (or “lily-like”) manner. In prime location directly next to the stand, a large free-standing wall featured clinical trial data for GLP-1 agonist Trulicity (dulaglutide) on one side and BI-partnered SGLT-2 inhibitor Jardiance (empagliflozin) on the other side. A little further from these prominent displays, smaller sections featured several other BI-partnered products, including SGLT-2 inhibitor/DPP-4 inhibitor Glyxambi (empagliflozin/linagliptin; with the Pixar-like duo from previous booths making a reappearance), DPP-4 inhibitor Tradjenta (linagliptin), and metformin combinations Synjardy (empagliflozin/metformin) and Jentadueto (linagliptin/metformin). The opposite end of Lilly’s booth devoted significant floor space to its Humulin U500 KwikPen, with the section featuring aqua tones to complement the pen’s aqua-colored body, in a departure from the red and white themes of the rest of the Lilly booth. Flanking the Humulin U500 KwikPen section were spaces devoted to biosimilar insulin glargine Basaglar (with prominent signage emphasizing that it would be available in the US on December 15, 2016) and the Humalog U200 KwikPen (featuring materials suggesting that patients would have to worry less about running out of insulin with the U200 formulation).

MannKind

MannKind occupied a small booth in the exhibit hall, but put forth a single loud-and-clear message: Afrezza is here to stay. A monitor on one side of the booth played a demonstration of Technosphere technology, while on the opposite side, an enlarged model of the Afrezza device was mounted to the wall. In the center was a simple slogan, written in playful purple font: “You know mealtime insulin. Let’s talk about Afrezza.” Pamphlets on Afrezza featured the slogan “OUTsulin” – a play on Afrezza’s disruptive approach to insulin.

Medtronic

Medtronic’s ample booth had several MiniMed 630G pumps on display, fresh off the approval just a day before AADE started (shipping in 6-7 weeks). It was impressive the pump made it into the booth at all, given the timing. A group of educators surrounded a rep to learn more about the new pump platform’s features, including the color screen, waterproof, remote bolusing from the Contour Next Link meter, and other additions discussed in last week’s report. There was a lot of excitement for the enhanced features, and many asked about the upgrade pathway for current Medtronic pumpers. Reps did not share specifics, but as we noted last week, it will be $599 or $3,100 out of pocket for current users (depends on whether the current pump was purchased after or before May 1, 2016, respectively; assumes the old pump is traded in for a $400 credit). The company confirmed with us separately that there will be a pathway for current Medtronic users to get on the 670G, though Medtronic has not worked out all the details yet. As we noted last week, however, the 630G cannot be software-updated to add the 670G algorithm. It will be fascinating to see how quickly the 630G sells, how quickly patients get on the 670G, and what early experiences are with the first commercialized hybrid closed loop system.

We ran through the 630G’s interface in the booth and several things jumped out:

The new navigation and screen is a definite improvement over current Paradigm pumps.

There are now four separate menus that can be accessed from the home screen (a bolus menu, a basal menu, a general pump menu, and a status menu) – we like that bolus and basal are very easy to access now, though the new layout is pretty multi-layered and will definitely require some learning. We have also heard this is true of the 670G.

Patients can stop a bolus midway through delivery (like Tandem’s t:slim). This is terrific to see, since it’s very easy to change one’s mind after hitting “Deliver.”

The bolus calculator fits very nicely on the larger screen and shows all the math line-by-line.

The pump carries doses to the thousandths place, impressive precision (especially for pediatrics). Some in the field might argue this is illusory precision (given bigger sources of error like carb counting), but it could appeal strongly to parents.

The 630G prominently shows the last entered blood glucose on the home screen when CGM is not being used.

The new platform is larger and a tiny bit heavier than previous Paradigm pumps. It will be interesting to see how patients trade off the curvier and mildly weightier design for the waterproof, color screen, and other new features. We think the company made the right call, but these nuances of product design are always very difficult.

Merck

In a spacious exhibit with plush, gray carpet, Merck highlighted with equal emphasis DPP-4 inhibitor Januvia (sitagliptin) and combination drug Janumet (sitagliptin/metformin). Large displays featured graphs depicting A1c lowering with each drug vs. metformin alone, while two tall, interactive monitors shared specific patient stories and additional data on the advantages of Januvia and Janumet. The only other product making an appearance was Pneumovax 23, a vaccine protecting against pneumococcal disease. Two small, outward-facing monitors displayed six patient scenarios to underscore the importance of the vaccine for people with chronic diseases such as diabetes.

mySugr

mySugr exhibited on US soil for the second time ever with big news: the limited US launch of mySugr Coaching in September – watch the inspiring and compelling video here, featuring educator extraordinaire Gary Scheiner (“Let’s be honest: doctors don’t have the ability to manage people’s blood sugars on a day to day basis.”). The product will have an introductory price of $19.99 per month ($39.99 ongoing), leverage the world’s most popular diabetes app (Logbook; 770,000+ registered users), and add a killer iPad Pro interface for diabetes educators (coaches) to view patient data and communicate seamlessly with users. Noted mySugr’s Scott Johnson: “I’ve got Gary Scheiner in my pocket.” We got a glimpse of the iPad interface in the company’s exhibit and were impressed – the company expects the chat-like interface will enable coaches to handle hundreds of patients at a time. Gary Scheiner and his colleagues Jennifer Smith and Lisa Foster-McNulty will be the first coaches on the platform, bringing incredible expertise to help the company refine the offering. The introductory launch in September will initially be for 200 patients, and if all goes well, expand from there.

We appreciated the company’s careful wording – “extend the reach of world-class educators like you” – positioning the app as an enabler for CDEs, not a replacement. We love the vision of “filling the gap between office visits” and giving patients “high-quality personalized diabetes education from the convenience of their smartphone.” In our view, human accountability + technology is where diabetes care must go to drive significant behavior change.

The mySugr team told us that educators like Gary waste a lot of time downloading data, a handicap that will be increasingly eliminated with this app – patients will take care of data input, with an increasing number of devices sending data automatically to the app (Roche’s Accu-Chek Connect BGM, Dexcom CGM via Apple Health, iHealth meters). More integrations are planned this year, and patients can also upload data from Abbott’s FreeStyle Libre and Medtronic’s Enlite via a web-interface (though the company sees this as an intermediate step.) Educators will have access to the data at their fingertips, eliminating cables, downloading, and wasted effort. The challenge, of course, will be if patients don’t enter any data at all, though this should be less of an issue with an out-of-pocket subscription model and accountability to a coach.

If mySugr Coaching drives strong outcomes, this model seems like a valuable option for payers and health systems. The service approach is where healthcare (and diabetes) seems to be going, and the use of technology to scale human expertise is the only option for diabetes care going forward – there are too many patients and too few providers for the status quo to continue.

mySugr now has a US headquarters in San Diego, and CEO Frank Westermann is even moving from Vienna! Now that’s a clear commitment to the stateside market from a company founded and based in Europe. We hope Logbook’s bolus calculator (only available in Europe now) comes here too – US patients do not have an FDA cleared option on the phone aside from Roche’s Accu-Chek Connect (meter required) and WellDoc’s BlueStar (prescription required).

Novo Nordisk

Novo Nordisk occupied two booths prominently featured at the center of the exhibit hall. The larger booth drew a bustling crowd intrigued by Novo Nordisk’s virtual reality game promoting next-generation basal insulin Tresiba (insulin degludec). Attendees donned headphones and a thick pair of black virtual reality goggles and sat turning their heads and rotating in low-slung white chairs along the booth’s periphery. The game featured a detailed and realistic 3D landscape that changed as the participant moved their eyes and rotated their body in space. In this virtual world, attendees could board a small plane, enjoy dynamic birds-eye views of the virtual landscape below, and finally sky dive to the ground below – all while coming across panes of information about Tresiba. The sky diving imagery incorporated well with Tresiba’s messaging in the booth, which lauded its ability to promote “proven A1c descent.” Tresiba dominated the booth’s floorspace and touchscreen displays by a wide margin. Peripheral signage referenced rapid-acting insulin NovoLog (insulin aspart) and GLP-1 agonist Victoza (liraglutide) but there was virtually no mention of Novo Nordisk’s older basal insulin analog Levemir (insulin detemir) or its obesity medication Saxenda (liraglutide 3.0 mg). The second, smaller booth was geared specifically toward CDEs, with a large blue sign overhead reading “Diabetes Educators.” At the center of the booth was a table where Novo Nordisk representatives sat, eager to offer perspective and commentary about Novo Nordisk’s products. Surrounding the table were large, rectangular touchscreen panels featuring patient vignettes and how different combinations of Novo Nordisk drugs fit their diabetes treatment needs.

OneDrop

OneDrop announced the upcoming launch of One Drop Premium: an impressive ~$30-40 per month cash pay for unlimited test strips, a Bluetooth-enabled BGM, 24/7 in-app CDE coaching, and a “digital therapeutics program” (AADE/ADA-based) in the One Drop app. The sharp One Drop Chrome meter (pictured below – we also tweeted about this late last week) is currently under FDA review, and we confirmed with CEO Jeff Dachis that the Premium service is expected to ship in October 2016 – on par with the goal as of SXSW, and impressively, just ~18 months after the app initially launched for iOS in April 2015. One Drop Android is expected to launch publicly in September, and the Premium service will be offered on both platforms – great to see, since most companies go iOS first, leaving many unable to access the benefits. One Drop’s accompanying Indiegogo crowdfunding campaign launched on July 25 and has already raised ~$25,000 – a testament to the interest in the consumer-product-feel and unlimited strips cash-pay model (less than the cost of a co-pay for many patients these days, and well less than the cost of a service that includes coaching). The meter, lancing device, 100-ct test strips, and vegan leather carrying case cost $65 alone, though purchasing a 12-month commitment to One Drop Premium costs only $395 ($33 per month) and includes the kit free. At the high end, a one-month commitment to One Drop Premium is ~$37 per month. CEO Jeff Dachis told us these pre-launch prices will stay roughly consistent once the platform launches this fall – if the economics work out, this would be highly impressive. OneDrop hasn’t disclosed the manufacturer of the meter and strips, but certain components look similar to the AgaMatrix Jazz 2 wireless meter and the original small profile iBGStar (this is our speculation, as neither company would confirm). We look forward to trying the platform and believe many can benefit from the low-cost unlimited strips, in-app coaching, and “look and feel” of the entire initiative.

A big focus at AADE was the provider side of the new platform, “One Drop Experts” (CDE coaching) and “One Drop Professional” (a population health management offering). One Drop Experts uses a browser-based interface enabling educators to chat with patients (near-time, asynchronous communication). Educators would see all data patients enter into the app, collected automatically (Bluetooth-enabled BGM integration, HealthKit, other devices) or manually inputted (e.g., insulin doses). From our view, the company seems well in line to leverage success through its broad-reaching data and systems – while the system “looks” cool, what’s cooler is the streamlined data and insight it will be able to share with patients. Indeed, OneDrop has said its goal is to be a Big Data company, and in line with this, the company is calling One Drop Professional a “population health management service” targeted at payers and HCPs – very smart.

Roche

A Roche rep shared that (i) there are no plans to bring the Accu-Chek Insight CGM to the US in the near future (launching by end of 2016 in the EU); and (ii) the next device in the US pipeline is the Medingo-acquired Solo patch pump, which is still at least a year out – we’re surprised to hear it is still in development! Most of the exhibit hall terrain was dedicated to the Accu-Chek line of meters, though it focused more on the digital features offered to users. Reps were excited to talk about Accu-Chek Connect, the Bluetooth-enabled BGM and paired app that includes a bolus calculator (launched in summer 2015). Anecdotally, patients utilizing the app have seen advances in their diabetes care, not to mention that the online portal makes it easier for clinicians to check in on their patients. There were no updates on the partnership with mySugr (announced in April), which is coming this fall according to mySugr’s blog. Another online tool designed to help patients is Accu-Chek Assist, a simple, yet time-saving web page that provides personalized estimates of out-of-pocket costs for test strips and setup instructions for the Connect BGM. But the main attraction of the booth was the “Target Toss Challenge” – visitors were encouraged to toss a suction cupped object at a graphic of an Accu-Chek Connect three-day report to win prizes (measuring spoons, measuring cups, portion plate, food model). Our favorite part of the game was the tagline off to the side that perfectly captured day-in, day-out glycemic management: “A game of skill and chance.”

Sanofi

Sanofi occupied two commanding booths at the center of the bustling exhibit hall. Sanofi’s main booth was calm and minimalist, as usual, and was sparsely attended compared to others in the exhibit hall. Sanofi dedicated the entirely of its booth to its varied insulin analog offerings. Some signage highlighted flagship Lantus (insulin glargine) and Apidra (insulin glulisine), but the vast majority of the booth’s floorspace was dedicated to next-generation basal insulin Toujeo (U300 insulin glargine). Several touchscreens provided interactive displays pointing to information on Toujeo’s efficacy in clinical studies and ease of use, and the perimeter of the booth was adorned with four-foot tall replicas of the Toujeo pen. GLP-1 agonist Adlyxin was nowhere to be found in the booth, perhaps because it was approved only a few weeks before AADE. Sanofi’s mountain-climbing-themed booth also made a reappearance, dominated by bright red signage and rugged rock walls, beneath large signs reading “Are you a glycemic explorer?” A humming crowd surrounded each of the touchscreens interspersed within the booth, eager to participate in the Glycemic Challenge multiple choice game, which quizzed attendees on little-known facts about insulin therapy for type 2 patients. For instance, one question read “How long do physicians typically wait to add insulin to therapy for patients with an A1c above 8%?” – the answer is a startling 6 years! A counter at the center of the booth filled with healthy, outdoorsy snacks like nuts, wasabi peas, and trail mix drew a substantial crowd as well.

Tandem

Tandem’s very spacious hardwood-floored booth promoted the company’s trifecta of pumps (t:slim, t:slim G4, t:flex), though our attention was drawn to the pipeline slides on the plasma screens flanking the booth. Reps confirmed the plan (as of the 2Q16 call two weeks ago) to launch the t:slim X2 pump in 4Q16. This pump will be nearly identical to the t:slim, but add a new two-way Bluetooth radio and manufacturing under class III controls. The latter will enable online software updates (via the newly cleared Tandem Device Updater) to add Dexcom G5 and G6 CGM integration and automated insulin delivery algorithms (predictive low glucose suspend, TypeZero hybrid closed loop algorithm). Tandem will be the first pump in the industry to offer this upgradeability, and its fully touchscreen interface (no buttons on the hardware) is a clear enabler on this front (easy to deploy different user interfaces, new menus, on-screen buttons, etc.). Tandem’s upcoming PLGS algorithm was “developed internally in consultation with industry thought leaders,” and the feasibility study at Stanford will be completed by the end of this month (as expected). From hallway conversations at AADE, we heard a lot of excitement from type-A patients about the t:slim X2 – the assured upgrade path (via software updates) de-risks the pump choice process as innovation begins moving at a faster clip.

Valeritas

The Valeritas booth was essentially identical to the one at ADA, presenting the V-Go and promising data from recently completed clinical trials. Valeritas recently cut back its sale force by >50% – a rep shared that the strategy is akin to hitting the reset button, and the company plans to reconstruct the force again, but surround them with more online and social media sales support. AADE was a “highly successful” conference for the company, with good-sized crowds congregating around its booth at multiple points. The rep could not comment on a potential EU launch, though we assume a distribution or manufacturing partnership is possible. CEO Mr. John Timberlake said on a call last week that the company will not establish infrastructure in Europe.

Walmart ReliOn

Walmart showcased its very low cost ReliOn brand of diabetes products. A rep shared that there will be a next-gen talking BGM available by next year for <$15, along with next-gen strips, which will use an alternative enzyme. There’s no doubt that the ReliOn products are cheap, but they have come under fire in the recent past for their accuracy, or lack thereof. In response, reps were handing out mini-posters detailing a study that compared the accuracy of the ReliOn Prime with the Abbott Freestyle Lite and the OneTouch Ultra 2. In the trial, the three BGMs were tested side-by-side on the same 180 study participants. The results suggested that the ReliOn Prime and Freestyle Lite were equally accurate, while the OneTouch Ultra 2 performed slightly worse. We wonder if the results will be published in a peer-reviewed journal.